A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes
A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes
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DOI：
10.1038/s41591-019-0415-5
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发表时间：
2019-05-01
期刊：
影响因子：
82.9
通讯作者：
Krolewski, Andrzej S.
中科院分区：
文献类型：
--
作者：
Niewczas, Monika A.;Pavkov, Meda E.;Krolewski, Andrzej S.
慢性炎症被假定参与糖尿病终末期肾病的发展，但哪些特定的循环炎性蛋白导致这种风险仍然未知。为了研究这一点，我们检测了来自3个独立队列的1型和2型糖尿病受试者的194种循环炎症蛋白。在每个队列中，我们发现了一种极其强大的肾脏风险炎症特征（KRIS），由富含肿瘤坏死因子受体超家族成员的17种蛋白质组成，与终末期肾病的10年风险相关。所有这些蛋白质都有全身性的非肾脏来源。我们的前瞻性研究结果提供了强有力的证据表明，KRIS蛋白有助于两种类型糖尿病终末期肾病发展的炎症过程。这些蛋白质指向新的治疗靶点和新的预后测试，以确定处于终末期肾病风险的受试者，以及测量对糖尿病肾病治疗反应的生物标志物。
Chronic inflammation is postulated to be involved in the development of end-stage renal disease in diabetes, but which specific circulating inflammatory proteins contribute to this risk remain unknown. To study this, we examined 194 circulating inflammatory proteins in subjects from three independent cohorts with type 1 and type 2 diabetes. In each cohort, we identified an extremely robust kidney risk inflammatory signature (KRIS), consisting of 17 proteins enriched in tumor necrosis factor-receptor superfamily members, that was associated with a 10-year risk of end-stage renal disease. All these proteins had a systemic, non-kidney source. Our prospective study findings provide strong evidence that KRIS proteins contribute to the inflammatory process underlying end-stage renal disease development in both types of diabetes. These proteins point to new therapeutic targets and new prognostic tests to identify subjects at risk of end-stage renal disease, as well as biomarkers to measure responses to treatment of diabetic kidney disease.